Method for stabilizing proteins with saccharide linked protein polymer conjugates

A method for stabilizing a protein in its native state to retain a functional property of the native protein in a hostile environment which without said stabilization would reduce said functional property, the method comprising covalently bonding the protein to a polymer to form a water soluble protein polymer conjugate, wherein the polymer is selected from the group consisting of a polyvinyl polymer, a polyester polymer, a polyamide polymer and mixtures thereof, the polymer having a main chain molecular weight of at least 5,000, and wherein three or more linker groups covalently bond both the protein and polymer and said linking groups have at least three hydroxyl groups and not more than 60 carbon atoms, each of said linker groups being selected from the group consisting of ##STR25## wherein E=--OH or --SH;

• n=0 or 1;
• W=0 or 1;
• and
• Y=bond or --CH.sub.2 ;
• wherein A is bonded to the polymer and is selected from the group consisting of ##STR26## B is bonded to the protein and is selected from the group consisting of ##STR27## wherein R.sub.1 and R.sub.2 are each selected from the group consisting of H, OH, acetoxy, alkoxy, phenylene, straight chain alkyl or branched chain alkyl having 1 to 12 carbons, ##STR28## wherein x=2 to 7, ##STR29## 2-hydroxy ethyl, 3-chloro-2-hydroxypropyl, 2-hydroxy-1-methylethyl, 2-hydroxypropyl, 3-hydroxypropyl, 2,3-dihydroxypropyl, 2 hydroxybutyl, 4-hydroxybutyl, diethylene-glycol, 5-hydroxypentryl, 6-hydroxyhexyl, triethyleneglycol, 7-hydroxyheptyl, 3,4-dihydroxybutyl, 5-hydroxypentyl, 6-hydroxyhexyl, 2,3-dimethyl-3-hydroxybutyl, 5,6-dihydroxyhexyl, 7-hydroxyheptyl, a residue of a mono-, di-, and trisaccharide;
• wherein R.sub.3 selected from the group consisting of H, straight chain alkyl or branched chain alkyl having 1 to 12 carbons, ##STR30## wherein x=2 to 7, ##STR31## 2-hydroxy ethyl, 3-chloro-2-hydroxypropyl, 2-hydroxy-1-methylethyl, 2-hydroxypropyl, 3-hydroxypropyl, 2,3-dihydroxypropyl, 2 hydroxybutyl, 4-hydroxybutyl, diethylene-glycol, 5-hydroxypentryl, 6-hydroxyhexyl, triethyleneglycol, 7-hydroxyheptyl, 3,4-dihydroxybutyl, 5-hydroxypentyl, 6-hydroxyhexyl, 2,3-dimethyl-3-hydroxybutyl, 5,6-dihydroxyhexyl, 7-hydroxyheptyl, a residue of a mono-, di-, and trisaccharide;
• and
• R'.sub.1, R'.sub.2, R'.sub.3, R'.sub.4, R'.sub.5, R'.sub.6, R'.sub.7, R'.sub.8, and R'.sub.9 each selected from the group consisting of H, OH, acetoxy, alkoxy, halogen and phosphate, straight chain alkyl or branched chain alkyl having 1 to 12 carbons, ##STR32## wherein x=2 to 7, ##STR33## 2-hydroxy ethyl, 3-chloro-2-hydroxypropyl, 2-hydroxy-1-methylethyl, 2-hydroxypropyl, 3-hydroxypropyl, 2,3-dihydroxypropyl, 2 hydroxybutyl, 4-hydroxybutyl, diethylene-glycol, 5-hydroxypentryl, 6-hydroxyhexyl, triethyleneglycol, 7-hydroxyheptyl, 3,4-dihydroxybutyl, 5-hydroxypentyl, 6-hydroxyhexyl, 2,3-dimethyl-3-hydroxybutyl, 5,6-dihydroxyhexyl, 7-hydroxyheptyl, a residue of a mono-, di-, and trisaccharide.